Introduction: Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several pathologies including cerebral ischemia, angiogenesis, inflammation and retinal degeneration. Aberrant STC1 expression has been reported in breast cancer but the significance is not clear.
Methods: High levels of STC1 expression were found in the aggressive 4T1 murine mammary tumour cells and in the MDA-MB-231 human breast cancer line. To investigate its significance, stable clones with STC1down-regulation were generated in both tumour models. The mRNA expression of these clones and clones with a non-silencing vector was checked by northern blotting or PCR and confirmed with western blotting for protein expression. The consequences of STC1 down-regulation on cell proliferation, chemotactic invasion, tumour growth and metastasis were assessed. Microarray gene expression analysis was also completed to identify genes altered by STC1 down-regulation.
Results: Down-regulation of STC1 in the 4T1 murine mammary tumour cells had a major impact on mammary tumour growth. This observation was replicated in a second tumour model with the MDA-MB-231 human breast cancer line, with a significant reduction in primary tumour formation and a major inhibition of metastasis as well. Notably, in both models, proliferation in vitro was not affected. Subsequent gene expression profiling identified 30 genes to be significantly altered by STC1 down-regulation, the majority of which are associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic analysis of breast cancer datasets revealed that high expression of STC1 is associated with poor survival.
Conclusion: This is the first study to show definitively that STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a potential therapeutic target for treatment of breast cancer patients